After decades of going after breast cancer with chemotherapy — the medical equivalent of a sledgehammer, smashing everything in its path — scientists are developing and deploying gentler, finer, more targeted tools that work better and cause fewer side effects. They’re learning how to blend and customize medications and treatment approaches for individual patients. And they’re reaching more patients with both early interventions and new treatments for advanced forms of metastasized breast cancer.
Their weapon in this effort: patients’ own immune systems.
“This is different from traditional therapies,” said Zahi Mitri, a breast cancer doctor and research scientist at the OHSU Knight Cancer Institute in Portland. “Instead of going after cancer cells, trying to kill them with chemicals, we want to unleash the power of the immune system.”
It’s the hottest topic in oncology today, Mitri said: boosting the body’s ability to do its natural work — either in concert with or, ideally, instead of chemotherapy, which often causes major side effects and stops working over time or doesn’t work at all.
In recent years, the U.S. Food and Drug Administration has approved several new immunotherapy treatments that target the most aggressive and hard-to-combat types of breast cancer.
One of these is triple-negative breast cancer, so-called because it lacks all three common “flags” that are usually present on tumor cells: estrogen, progesterone and HER2, a growth-promoting protein.
When those flags are present, you can fight the cancer with targeted drugs and hormone therapies, Mitri said. When they’re not, “you’re stuck with chemotherapy,” he said.
Now, he said, the FDA has approved combination immunotherapy-chemotherapy approaches. A treatment for patients with advanced, metastatic stage 4 triple-negative breast cancer was approved a few years ago. Just a few months ago, the FDA approved a treatment for early-stage triple-negative, he said.
“That’s exciting because we feel our best chance of curing a breast cancer is as soon as we encounter it. Adding immunotherapy to chemotherapy, the proportion of people we can cure has gone up,” Mitri said.
Tricky signals
Since some cancers trick the immune cells into hitting the brakes with false signals, immunotherapies called checkpoint inhibitors work by retraining the immune system to classify cancer cells as foreign invaders, Mitri said.
“Tumors have a way of blocking immune cells with signals that say, ‘Don’t attack me.’ We can use immunotherapy to lower those inhibitions again,” he said.
That avoids the hardcore side effects of chemotherapy, but what can happen instead is autoimmune side effects, including thyroid problems that sometimes require hormone therapy, too. Even more unfortunately, tumors still sometimes return after initial treatment, and some therapies seem to stop working, Mitri said.
“We work with a lot of metastatic cases that are in need of new treatments,” he said. “If we are dealing with stage 4, triple negative, and we are using new therapies, how can we make sure we are giving each person the right treatment?”
One way is by getting SMMART, which stands for Serial Measurements of Molecular and Architectural Responses to Therapy. That’s a flagship cancer treatment program at OHSU, focused on customizing the best possible therapy for each triple-negative patient. It combines new drug trials, real-time treatment adaptation and careful patient monitoring, Mitri said.
“To do all that,” he said, “you need the right combination of people seeing the patient and making good judgments about the next step forward — and you need people in the lab who are working to develop the next test down the line, moving science forward.”
Mitri said the effort is bearing fruit.
“I do think there’s a lot of progress being made. We’ve had three approvals of new therapies in the past two years. The box of options we’ve got for patients is expanding rapidly,” he said.
Still, immunotherapy alone has not shown the same benefit for hormone-driven breast cancers, which make up the large majority of breast cancer cases, he said.
“We may not have found the right combination of therapies,” Mitri said. “We have ongoing studies of targeted combinations for hormone-driven breast cancer and early-stage disease.”
The last few years have seen the FDA speed up its drug-approval process, Mitri added.
“The timeline was shortened, even before the pandemic,” he said. “The FDA has made a conscious effort to allow earlier access for patients when the data is there. At the same time, they have maintained the same level of rigor with regard to safety. That’s huge because we are responsible for our patients, and we never want to forget that.”
